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  • Review Article
  • Published:

Knowing your friends: invertebrate innate immunity fosters beneficial bacterial symbioses

Nature Reviews Microbiology volume 10, pages 815–827 (2012)Cite this article

Subjects

Key Points

  • Traditionally, it has been thought that the main function of the innate immune system is to combat pathogens. However, accumulating evidence supports the idea that the immune system also serves an important role in establishing and maintaining beneficial symbioses between the host and the microbiota.

  • Four model invertebrate animal systems that form stable, long-term associations with bacterial symbionts — the cnidarian Hydra spp., the bobtail squid, the medicinal leech and the pea aphid — highlight how the innate immune system shapes these symbioses. On the basis of studies using these models, we propose mechanisms by which symbionts and non-symbionts can be distinguished by these hosts.

  • Many of these interactions are mediated through symbiont-derived microorganism-associated molecular patterns (MAMPs) and host-derived pattern recognition receptors (PRRs), which lead to downstream host signalling events and the regulation of host immune effectors.

  • In several of the model systems, the cellular immune response, in the form of phagocytic haemocytes, plays an important part in mediating interactions with symbionts. In some invertebrates, these cells can distinguish between symbiotic and non-symbiotic bacteria, and some symbionts might also have mechanisms for avoiding phagocytosis.

  • Acellular, chemical effectors such as antimicrobial peptides and reactive oxygen species can also have important roles in determining the composition of the microbial community.

  • We propose three mechanisms by which invertebrate hosts can distinguish between symbionts and non-symbionts: reciprocal signalling involving MAMPs and PRRs; sequestration of symbionts to specialized organs, tissues and cells; and avoidance of integrating a MAMP response with a damage signal, which otherwise leads to a heightened immune response by the host.

Abstract

The innate immune system is present in all animals and is a crucial first line of defence against pathogens. However, animals also harbour large numbers of beneficial microorganisms that can be housed in the digestive tract, in specialized organs or on tissue surfaces. Although invertebrates lack conventional antibody-based immunity, they are capable of eliminating pathogens and, perhaps more importantly, discriminating them from other microorganisms. This Review examines the interactions between the innate immune systems of several model invertebrates and the symbionts of these organisms, and addresses the central question of how these long-lived and specific associations are established and maintained.

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Figure 1: Model systems of invertebrate symbioses.
Figure 2: Proposed pathways of innate immune response activation in invertebrates.
Figure 3: Model for the establishment of symbiostasis in host–microorganism associations.

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Acknowledgements

The authors thank the anonymous reviewers for helpful suggestions. Research in the S.V.N. laboratory was supported by the US National Science Foundation (NSF) (grant IOS-0958006) and the University of Connecticut Research Foundation. Research in the J.G. laboratory was supported by the NSF (Career Award MCB 0448052), the US National Institutes of Health (grant RO1 GM095390) and the University of Connecticut Research Foundation.

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    Spencer V. Nyholm & Joerg Graf

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    Spencer V. Nyholm & Joerg Graf

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Glossary

Symbiont

As used in this Review: a microorganism that forms a specific, stable and beneficial association with a particular host. Although this is now a commonly accepted definition, the original definition of symbionts, by Anton de Bary, included pathogenic, commensal and mutualistic symbionts.

Pattern recognition receptors

Eukaryotic proteins that bind to microorganism-associated molecular patterns, activating downstream signalling and, ultimately, innate immunity effector responses. Examples include Toll-like receptors, peptidoglycan recognition proteins and Gram-negative bacteria-binding proteins.

Peptidoglycan

The polymer that makes up the bacterial cell wall, and consists of β-(1-4)-linked N-acetylglucosamine and N-acetylmuramic acid linked to small peptide chains.

Lipopolysaccharide

A major component of the outer membrane of Gram-negative bacteria. It is composed of an O antigen, a core oligosaccharide and lipid A.

Outer-membrane proteins

Proteins that are common to the outer membrane of Gram-negative bacteria.

Flagellins

Bacterial major flagellar proteins.

Type III secretion system

A needle-like secretion system that allows Gram-negative bacteria to inject toxins directly into eukaryotic cells.

Microorganism-associated molecular patterns

Molecular motifs that are unique to microorganisms (both pathogens and non-pathogens) and are often recognized by components of the innate immune system.

Toll-like receptors

(TLRs). A diverse group of evolutionarily conserved pattern recognition receptors that are characterized by extracellular leucine-rich repeats and a cytoplasmic Toll–interleukin-1 receptor motif. Binding of microorganism-associated molecular patterns to TLRs often leads to downstream signalling via the nuclear factor-κB pathway or related pathways and results in the regulation of immune effectors.

Peptidoglycan recognition proteins

Eukaryotic proteins that can bind and sometimes degrade bacterial peptidoglycan, and are expressed in various locations within a cell.

Endoymbioses

As used in this Review: associations between hosts and intracellular symbionts (endosymbionts). These symbionts fall into two groups: obligate or primary symbionts, which are always found associated with the host, and secondary symbionts, which are not always present.

Complement system

A humoral component of the innate immune system; the complement pathway leads to the opsonization of microorganisms. There are three types of complement pathway: classical, alternative and lectin.

Nuclear factor-κB pathway

An evolutionarily conserved signalling cascade involving multiple protein complexes that control the transcription of immunity genes.

Damage-associated molecular pattern

A host-derived non-microbial factor that is released following tissue damage or necrosis and can activate the immune system in a similar way to microorganism-associated molecular patterns.

Toll–interleukin-1 receptor domain

A cytosolic domain that is common to a diverse group of receptors, including Toll and Toll-like receptors, and is found in proteins of the basal Hydra spp. discussed in this Review.

Expressed sequence tag

(EST). A cDNA sequence that has been obtained from a reverse-transcribed mRNA.

Immune deficiency pathway

An immune pathway that is found in most insects and responds to bacteria via peptidoglycan recognition proteins binding to diaminopimelic acid-containing peptidoglycan. Subsequent signalling pathways can lead to AMP production.

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Nyholm, S., Graf, J. Knowing your friends: invertebrate innate immunity fosters beneficial bacterial symbioses. Nat Rev Microbiol 10, 815–827 (2012). https://doi.org/10.1038/nrmicro2894

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